Trizivir Vs. Kaletra and Combivir for the Prevention of Mother-to-Child Transmission of HIV

• Virologic suppression [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Infant's HIV status [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  

• HIV-1 RNA levels in plasma and breast milk [ Time Frame: At study entry and Months 1, 3, and 5 ] [ Designated as safety issue: No ]
  
• HIV-1 DNA levels in breast milk [ Time Frame: At Months 1, 3, and 5 ] [ Designated as safety issue: No ]
  
• Time from randomization to the first adverse event requiring discontinuation of any of the drugs that formed the initial regimen by treatment arm and compared to Mashi study [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Time from randomization to the first Grade 3 or higher adverse event by treatment arm and compared to Mashi study [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• Occurrence of Grade 3 or higher adverse events by type, grade, body system, and association with study treatment compared to Mashi study [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• Premature birth and very premature birth, defined as 37 and 32 weeks gestation or less, respectively [ Time Frame: At study entry ] [ Designated as safety issue: No ]
  
• Low birth weight and very low birth weight, defined as less than 2,500 g and less than 1,500 g, respectively [ Time Frame: At study entry ] [ Designated as safety issue: No ]
  
• Growth and developmental delay, defined as standard norms and neurodevelopmental screening [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• Maternal mortality [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• Maternal morbidity, defined as occurrence of Grade 3 or 4 adverse events, hospitalizations, and AIDS-defining or AIDS-associated diagnoses [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• Change in maternal CD4 count from baseline over time [ Time Frame: Through Month 24 ] [ Designated as safety issue: No ]
  
• Infant mortality [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• Comparison of neurodevelopment at 2 years of age in the Mashi study and this study [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Adherence, as measured by questionnaire and pill count [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Occurrence of HIV-1 RNA genetic mutations associated with viral resistance in maternal plasma and breast milk and infant plasma among transmitting mother-infant pairs at the nearest time to transmission [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Antiretroviral therapy (ARV) toxicities and viral load differences by maternal HLA type, for subset of up to 500 women with HLA-type available [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• ARV concentrations in breast milk and serum and in their infants' serum for all transmitting mother-infant pairs and a matched group of nontransmitting pairs [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  

While perinatal HIV infection has become rare in developed countries through the use of highly active antiretroviral therapy (HAART), it remains a serious problem in developing countries. Botswana has a population of approximately 1.7 million; the prevalence of HIV in Botswana is about 37.4%. In the developed world, HAART has revolutionized the prevention of MTCT among nonbreastfed infants. This trial will compare the effectiveness of a protease inhibitor (PI)-based regimen versus a triple nucleoside reverse transcriptase inhibitor (NRTI)-based regimen in preventing MTCT of HIV.

This study will last up to 24 months for mothers and their children. Participants will be stratified based on their CD4 count at screening. Women with CD4 counts of 200 cells/mm3 or more will be in one of two treatment groups and will be randomly assigned to receive either TZV twice daily or LPV/RTV and 3TC/ZDV twice daily. Once in labor, treatment group participants will continue to take their assigned HAART regimen and will also be given additional ZDV. Women with CD4 counts less than 200 cells/mm3 will receive nevirapine (NVP) once daily for the first 14 days, then twice daily, and 3TC/ZDV twice daily; these women will be in the observational group.

Shortly after birth, infants will receive single-dose NVP. A 1-month supply of ZDV will be provided to the mother to administer daily to her child. Mothers will stop HAART at 6 months postpartum or when they stop breastfeeding, whichever occurs earlier. A clinical evaluation, blood collection, and HIV prevention counseling will occur at all maternal visits. An obstetrical exam and physical exam will occur at selected visits. Women will provide at least four samples of breast milk during the first 5 months postpartum. For infants, a clinical evaluation will occur at every visit, and a physical exam and blood collection will occur at selected visits.